For obtaining optically-active piperidine derivatives, their racemates may be subjected to optical resolution. However, its theoretical yield is 50% of the racemates, and the process is unsatisfactory for industrial use. Therefore, if unnecessary optical antipodes could be racemized and recycled for the starting materials for optical resolution, the yield of the intended optically-active piperidine derivatives would be approximately 100% in theory. Accordingly, racemization of optically-active piperidine derivatives to give racemic piperidine derivatives is an important technique. However, no one knows at all a method for racemizing optically-active piperidine derivatives of general formulae (1), (2) and (3): wherein R1 represents a lower alkyl group having from 1 to 4 carbon atoms, a phenyl group, or an aralkyl group; R2, R3 and R4 may be the same or different, each representing a hydrogen atom, an alkyl group, a phenyl group, an aralkyl group, an alkoxycarbonyl group, an alkylsulfonyl group, an arylsulfonyl group, an aralkylsulfonyl group, or an acyl group; R5 represents an alkyl group, a phenyl group, an aralkyl group, an alkoxycarbonyl group, an alkylsulfonyl group, an arylsulfonyl group, an aralkylsulfonyl group, or an acyl group.
On the other hand, for producing optically-active 3-[3-(methylsulfonyl)phenyl]-1-propylpiperidine, for example, known are a method of deriving it from optically-active 3-(3-hydroxyphenyl)-1-propylpiperidine (J. Med. Chem., 1994, 37, 2735-2753); and a method that comprises optically resolving racemic 3-[3-(methylsulfonyl)phenyl]piperidine with optically-active tartaric acid followed by reacting the resulting product with propionaldehyde and reducing it (Tetrahedron Letters, Vol. 35, No. 48, 9063-9066).
However, the method of deriving the compound from optically-active 3-(3-hydroxyphenyl)-1-propylpiperidine often involves racemization as it includes multiple steps in which the compounds being processed are kept all the time optically active, and its yield to give the intended optically-active 3-[3-(methylsulfonyl)phenyl]-1-propylpiperidine of high optical purity is low.
In the method that comprises optically resolving racemic 3-[3-(methylsulfonyl)phenyl]piperidine with optically-active tartaric acid followed by deriving the intended compound from the resulting intermediate, the yield of optical resolution is low and, in addition, the optical purity of optically-active 3-[3-(methylsulfonyl)phenyl]piperidine is low.